Arthritic disorders are the second leading cause of losses in time and earnings in the United States. Approximately six million (6,000,000) people are afflicted with rheumatoid arthritis. Of these, over eighty percent (80%) ultimately will have involvement of the hand joint, over fifty percent (50%) will involve the knee joint, and somewhat smaller percentages will have involvement of other joints such as the ankle, elbow, and shoulder. Rheumatoid arthritis is believed to be an autoimmune disease wherein parts of the body are attacked by antibodies manufactured in the body. These antibodies may be produced in response to viruses present in the body. While the mechanism for rheumatoid arthritis is not known, it is a systemic disease. When the disease is active, the erythrocyte sedimentation rate (ESR) is usually elevated and the blood tests usually positive for rheumatoid factor.
A source of disability for the sufferer of rheumatoid arthritis is an inflammatory response, of unknown origin, in the synovium, or lining, of the afflicted joint. This chronic inflammation, or synovitis, leads to pannus formation and eventually, destruction of the joint cartilage.
Presently, the primary method of treating rheumatoid arthritis is by use of compounds directed at blocking the inflammatory process. These compounds include aspirin, penicillamine, gold salts, and many other ethical drugs. Unfortunately these attempts are often unsuccessful and the relief provided is temporary at best. In the knee, a primary alternative is the surgical excision of the inflamed synovium in a procedure known as surgical synovectomy. In this procedure, the abnormal synovium and pannus formation are surgically removed. While in many cases this procedure proves to arrest the disease, it also has a significant number of drawbacks and limitations. Among these are limitations on complete removal of the inflamed synovium, the risks and dangers inherent in the operation itself; and the required lengthy recovery period, much of which is spent in the hospital.
However, surgical procedures to treat rheumatoid synovitis of the phalangeal joints or of the metacarpo-phalangeal joints is not satisfactorily done. Thus the development of a suitable agent for treating rheumatoid synovitis of these interphalangeal or metacarpo-phalangeal joints is of significance. This is the basis for utilizing Tin, Sn-121.
In order to overcome these problems, attempts have been made to destroy the diseased synovium by the performance of a procedure known as radiation synovectomy. Intra-articular injection of colloidal gold-198 (.sup.198 Au) has bsen reported to abate inflamed synovium (Fellinger et al, 33 WEIN Z. INN, Med. 351, (1952) and Ansell et al, 22 Ann. Rheum. Dis. 435 (1963). Unfortunately this procedure is disadvantageous due to the small particle size of the gold colloid utilized and the high energy gamma emitted during decay (gamma emission). This emission poses dangers to the patient by increasing the whole body dose, thereby exposing healthy tissue to radiation, and posing substantial difficulties with radiation protection for hospital personnel.
The use of other radionuclides has also been attempted in radiation synovectomy. These radionuclides include Erbium-169 (.sup.169 Er) as reported in Menkes et al, 36 Ann. Rheum. Dis. 254 (1977); Rhenium-186 (.sup.186 Re) as reported in Deckart et al, 3 Radiobiol, Radiother 363 (1979) and in DelBarre et al, 2 Nouv. Presse. Med 1372 (1973); Phosphorus-32 (.sup.32 P) as reported in Wenston et al, 14 J. Nuc. Med 886 (1973), and Yttrium-90 (90Y) as reported in Gumpel et al, 48 Br. J. Radiol. 377 (1975).
Each of these radionuclides (.sup.169 Er, .sup.186 Re, .sup.32 P, .sup.198 Au, and .sup.90 Y) has proven disadvantageous due to either the long physical half-life of the particular radionuclide involved, the small particle size of the system, and/or the occurrence of significant amounts of radioactivity leaking from the affected joints and associated chromosomal aberrations in the lymphocytes of the patient. (See also; Oka et al, 17 Acta Rheum. Scand. 148 (1971) and Virkkunen et al, 13 Acta Rheum., Scand., (1967).
Currently the preferred radionuclide for the interphalangeal or metacarpo-phalangeal joints is .sup.169 Er in various forms. Its disadvantages however include an excessively long physical half-life of 9.4 days. Many physicians would not utilize a preparation with such a long half-life in treating rheumatoid synovitis.
Because the synovial space associated with the proximal interphalangeal or metacarpo-phalangeal joints, the emission energy of the radionuclide must be significantly lower than the agents that would be utilized to treat the larger knee joint. Hence .sup.90 Y, .sup.198 Au, .sup.165 Dy, or .sup.166 Ho are not attractive agents in this application involving interphalangeal or metacarpo-phalangeal joints. Tin, Sn-121 possesses excellent nuclear properties for treating these joints. The properties include half-life of 27 hours, low energy beta emission, and no gamma photons. In addition, the chemistry of Tin, (Sn) is well known and is useful in the preparation of the compound incorporating Tin, Sn-121.